The Role of M1/M2 Macrophage Polarization in Rheumatoid Arthritis Synovitis

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: May 19, 2022

Innate and adaptive immunity represent a harmonic counterbalanced system involved in the induction, progression, possibly resolution of inflammatory reaction that characterize autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis (RA). Although immunopathophysiological mechanisms ARDs are not fully clarified, they often associated with an inappropriate macrophage/T-cell interaction, where classical (M1) or alternative (M2) macrophage activation may influence occurrence T-helper (Th)1 Th2 responses. In RA patients, M1/Th1 occurs environment dominated by Toll-like receptor (TLR) interferon (IFN) signaling, it promotes massive production pro-inflammatory cytokines [i.e., tumor necrosis factor-α (TNFα), interleukin (IL)-1, IL-12, IL-18, IFNγ], chemotactic factors, matrix metalloproteinases resulting osteoclastogenesis, erosion, progressive joint destruction. On other hand, M2/Th2 response determines release growth factors IL-4, IL-10, IL-13, transforming factor (TGF)-β] anti-inflammatory process leading to clinical remission RA. Several subtypes macrophages have been described. Five polarization states from M1 M2 confirmed vitro studies analyzing morphological characteristics, gene expression phenotype markers (CD80, CD86, TLR2, TLR4, CD206, CD204, CD163, MerTK), functional aspect, reactive oxygen species (ROS). An imbalance induce pathological consequences contribute several diseases, such as asthma osteoclastogenesis patients. addition, dynamic includes presence intermediate polarity stages distinguished specific surface production/release distinct molecules (i.e., nitric oxide, cytokines), which their state. This suggests "continuum" playing important role during inflammation its resolution. review discusses importance delicate M1/M2 different phases together identification pathways, cytokines, chemokines involved, outcomes The analysis these aspects could shed light on abnormal activation, novel therapeutical approaches restore balance.

Language: Английский

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Macrophages: The Good, the Bad, and the Gluttony

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Aug. 12, 2021

Macrophages are dynamic cells that play critical roles in the induction and resolution of sterile inflammation. In this review, we will compile interpret recent findings on plasticity macrophages how these contribute to development non-infectious inflammatory diseases, with a particular focus allergic autoimmune disorders. The inflammation then be examined, emphasizing ability clear apoptotic immune cells. Rheumatoid arthritis (RA) is chronic autoimmune-driven spectrum diseases where persistent results synovial hyperplasia excessive cell accumulation, leading remodeling reduced function affected joints. central pathophysiology RA, driving episodic cycles tissue destruction. RA patients have increased numbers active M1 polarized pro-inflammatory few or inactive M2 type This imbalance macrophage homeostasis main contributor mediators resulting continual activation stromal populations accelerated remodeling. Modulation phenotype remains key therapeutic goal for treatment disease. Intriguingly, intervention glucocorticoids other DMARDs promotes re-polarization an anti-inflammatory phenotype; reprogramming dependent metabolic changes promote phenotypic switching. Allergic asthma associated Th2-polarised airway inflammation, structural large airways, hyperresponsiveness. Macrophage polarization has profound impact pathogenesis, as response allergen exposure regulated by intricate interplay between local factors including cytokines, chemokines danger signals from neighboring Th2-polarized environment characteristic asthma, high levels IL-4 produced locally infiltrating innate lymphoid helper T acquisition alternatively activated M2a macrophages, myriad effects structure. Targeting regulators currently being pursued diseases. re-balancing responses towards pro-resolution thus success response. It long been established apoptosis supports monocyte recruitment sites facilitating subsequent corpse clearance. drives mediates switch polarity macrophages. However, role cell-derived extracellular vesicles (ACdEV) control received remarkably little attention. ACdEV powerful intercellular communication, carrying wealth lipid protein may modulate phenotype, cargo immune-modulating enzymes. such interactions result repair disease different contexts. discuss origin, characterization, activity underlying mechanisms via clearance, order provide new insights into strategies could exploit capabilities agile responsive

Language: Английский

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Recent Advances in Understanding the Pathogenesis of Rheumatoid Arthritis: New Treatment Strategies

Cells, Journal Year: 2021, Volume and Issue: 10(11), P. 3017 - 3017

Published: Nov. 4, 2021

Rheumatoid arthritis (RA) is considered a chronic systemic, multi-factorial, inflammatory, and progressive autoimmune disease affecting many people worldwide. While patients show very individual courses of disease, with RA focusing on the musculoskeletal system, joints are often severely affected, leading to local inflammation, cartilage destruction, bone erosion. To prevent joint damage physical disability as one symptoms RA, early diagnosis critical. Auto-antibodies play pivotal clinical role in systemic RA. As biomarkers, they could help make more efficient diagnosis, prognosis, treatment decision. Besides auto-antibodies, several other factors involved progression such epigenetic alterations, post-translational modifications, glycosylation, autophagy, T-cells. Understanding interplay between these would contribute deeper insight into causes, mechanisms, progression, disease. In this review, latest research findings discussed better understand pathogenesis, finally, strategies for therapy presented, including both conventional approaches new methods that have been developed recent years or currently under investigation.

Language: Английский

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Biological drug and drug delivery-mediated immunotherapy

Acta Pharmaceutica Sinica B, Journal Year: 2020, Volume and Issue: 11(4), P. 941 - 960

Published: Dec. 31, 2020

The initiation and development of major inflammatory diseases, i.e., cancer, vascular inflammation, some autoimmune diseases are closely linked to the immune system. Biologics-based immunotherapy is exerting a critical role against these whereas usage immunomodulators always limited by various factors such as susceptibility digestion enzymes in vivo, poor penetration across biological barriers, rapid clearance reticuloendothelial Drug delivery strategies potent promote their delivery. Herein, we reviewed potential targets for discussed biologics drug systems involved immunotherapy, particularly highlighted approved therapy tactics, finally offer perspectives this field.

Language: Английский

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Novel insights into macrophage diversity in rheumatoid arthritis synovium

Autoimmunity Reviews, Journal Year: 2021, Volume and Issue: 20(3), P. 102758 - 102758

Published: Jan. 19, 2021

Language: Английский

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Human Gut Microbiota and Its Metabolites Impact Immune Responses in COVID-19 and Its Complications

Gastroenterology, Journal Year: 2022, Volume and Issue: 164(2), P. 272 - 288

Published: Sept. 23, 2022

Background & AimsWe investigate interrelationships between gut microbes, metabolites, and cytokines that characterize COVID-19 its complications, we validate the results with follow-up, Japanese 4D (Disease, Drug, Diet, Daily Life) microbiome cohort, non-Japanese data sets.MethodsWe performed shotgun metagenomic sequencing metabolomics on stools cytokine measurements plasma from 112 hospitalized patients SARS-CoV-2 infection non–COVID-19 control individuals matched by important confounders.ResultsMultiple correlations were found COVID-19–related microbes (eg, oral short-chain fatty acid producers) metabolites branched-chain aromatic amino acids, carbohydrates, neurotransmitters, vitamin B6). Both also linked to inflammatory dynamics interferon γ, λ3, interleukin 6, CXCL-9, CXCL-10). Such detected highly in severe disease pneumonia; moderately high D-dimer level, kidney dysfunction, liver dysfunction groups; but rarely diarrhea group. We confirmed concordances of altered spermidine, putrescine, B6) their corresponding microbial functional genes. Results metabolomic alterations cross-sectional set partly concordant those follow-up set. Microbial signatures for distinct diabetes, bowel disease, proton-pump inhibitors overlapping rheumatoid arthritis. Random forest classifier models using microbiomes can predict disease. The showed moderate concordance Hong Kong Japan.ConclusionsMultiomics analysis revealed multiple microbe-metabolite-cytokine COVID-19related complications few gastrointestinal suggesting microbiota-mediated immune responses organ sites. Our underscore existence a gut-lung axis COVID-19. sets. confounders. Multiple Japan. Multiomics

Language: Английский

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Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: April 12, 2022

Abstract Immune checkpoint inhibitors are associated with immune-related adverse events (irAEs), including arthritis (arthritis-irAE). Management of arthritis-irAE is challenging because immunomodulatory therapy for should not impede antitumor immunity. Understanding the mechanisms critical to overcome this challenge, but pathophysiology remains unknown. Here, we comprehensively analyze peripheral blood and/or synovial fluid samples from 20 patients arthritis-irAE, and unmask a prominent Th1-CD8 + T cell axis in both inflamed joints. CX3CR1 hi CD8 cells CXCR3 fluid, most clonally expanded cells, significantly share TCR repertoires. The migration into joints possibly mediated by CXCL9/10/11/16 expressed myeloid cells. Furthermore, after combined CTLA-4 PD-1 inhibitor preferentially has enhanced Th17 transient Th1/Th17 signatures. Our data provide insights mechanisms, predictive biomarkers, therapeutic targets arthritis-irAE.

Language: Английский

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Cytokines as Key Players in Obesity Low Grade Inflammation and Related Complications

Obesity Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 100585 - 100585

Published: Jan. 1, 2025

Language: Английский

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CXCL10 Chemokine: A Critical Player in RNA and DNA Viral Infections

Viruses, Journal Year: 2022, Volume and Issue: 14(11), P. 2445 - 2445

Published: Nov. 3, 2022

Chemokines constitute a group of small, secreted proteins that regulate leukocyte migration and contribute to their activation. are crucial inflammatory mediators play key role in managing viral infections, during which the profile chemokine expression helps shape immune response clearance, improving clinical outcome. In particular, ligand CXCL10 its receptor CXCR3 were explored plethora RNA DNA infections. this review, we highlight CXCL10/CXCR3 axis host defense against variety We also discuss interactions among viruses cells trigger expression, as well signaling cascades induced positive cells.

Language: Английский

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Osteopontin: A Bone-Derived Protein Involved in Rheumatoid Arthritis and Osteoarthritis Immunopathology

Biomolecules, Journal Year: 2023, Volume and Issue: 13(3), P. 502 - 502

Published: March 9, 2023

Osteopontin (OPN) is a bone-derived phosphoglycoprotein related to physiological and pathological mechanisms that nowadays has gained relevance due its role in the immune system response chronic degenerative diseases, including rheumatoid arthritis (RA) osteoarthritis (OA). OPN an extracellular matrix (ECM) glycoprotein plays critical bone remodeling. Therefore, it effector molecule promotes joint cartilage destruction observed clinical studies, vitro assays, animal models of RA OA. Since undergoes multiple modifications, posttranslational changes, proteolytic cleavage, binding wide range receptors, by which produces effects, some cases, remain unclear. Although there strong evidence contributes significantly immunopathology OA when considering as common denominator molecule, experimental trial results argue for protective rheumatic diseases. Elucidating detail involvement degeneration interest field rheumatology. This review aims provide OPN’s multifaceted promoting propose AR immunopathology.

Language: Английский

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